Potassium tert-butoxide → Bimatoprost

Temperatur

0 °C

(5-(Ethylamino)-5-oxopentyl)triphenylphosphonium bromide 96 (1.37 g, 2.91 mmol, 6 eq.) was added to a flame dried Schlenk flask, under N2, and anhydrous THF (10 ml) added. The resulting suspension was cooled to 0° C. KOt-Bu (653.0 mg, 5.82 mmol, 12 eq.) was added in one portion and the resulting orange mixture stirred at 0° C. for 40 min. A solution of crude triol 94 (0.485 mmol, 1 eq.) in anhydrous THF (2.5 ml) was added dropwise via syringe. After complete addition the mixture was stirred at r.t. for 1 h. The reaction was quenched with saturated aq. NH4Cl (10 ml) and extracted with EtOAc (5×10 ml). The combined organic phases were dried (MgSO4), filtered, and concentrated to give the crude material as solids. These were triturated with EtOAc (10 ml) and the solids filtered and washed with EtOAc (4×10 ml). The filtrate was concentrated under vacuum and purified by column chromatography on silica, eluting with EtOAc/MeOH (97.5:2.5 to 95:5) to give 97 (99.2 mg) as a yellowish oil which was further purified by preparative TLC (EtOAc/MeOH 5%) to give 97 (82.6 mg, 41% over 2 steps) as a clear, colourless oil. Analytical data consistent with the literature (Zanoni, G. et al., Tetrahedron 66, 7472-7478 (2010); Gutman, A. et al., US 20090163596 (2009)).

1. customdried Schlenk flask
2. additionunder N2, and anhydrous THF (10 ml) added
3. additionAfter complete addition the mixture
4. stirringwas stirred at r.t. for 1 h
5. customThe reaction was quenched with saturated aq. NH4Cl (10 ml)
6. extractionextracted with EtOAc (5×10 ml)
7. dry with materialThe combined organic phases were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto give the crude material as solids
11. customThese were triturated with EtOAc (10 ml)
12. filtrationthe solids filtered
13. washwashed with EtOAc (4×10 ml)
14. concentrationThe filtrate was concentrated under vacuum
15. custompurified by column chromatography on silica
16. washeluting with EtOAc/MeOH (97.5:2.5 to 95:5)

ORD-Eintrag

ord-015d5d56d5d84b12a391046e0c2846d6

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09242954B2